The genetically engineered mice require special husbandry care and are mainly housed in Individually Ventilated Cage (IVC) systems and Static Micro Isolator Cages (SMIC) to minimize the risk for spreading undesirable microorganisms. However, the static micro isolation cage housing like SMIC are being replaced with IVC systems in many facilities due to a number of benefits like a higher density housing in limited space, better protection from biohazards and allergens and decreased work load due to decreased frequency of cage changing required in this system. The purpose of this study was to examine the reproductive performance of genetically engineered mice housed in individually ventilated cages (IVC) and Static Micro Isolator Cages (SMIC). When the B6C3-Tg (APPswe, PSEN1dE9) 85Dbo/Mmjax transgenic mice were housed in these two housing systems, the number of litters per dam, number of pups born per dam and number of pups weaned per dam were found to be slightly higher in the IVC as compared to the SMIC but the difference was not significant (P<0.05). In case of Growth Associated Protein 43 (GAP-43) knockout mice, the number of litters born per dam and the number of pups born per dam were marginally higher in the IVC as compared to those housed in SMIC but the difference was not significant (P<0.05). Only the number of pups weaned per dam were found to be significantly higher as compared to those housed in the SMIC system at P<0.05.
Allergens ; Animals ; GAP-43 Protein ; Hazardous Substances ; Housing* ; Mice* ; Mice, Knockout ; Mice, Transgenic

Telomeres serve a critical role in maintenance of genomic stability in all eukaryotes, from yeast to human. The maintenance of telomeres is achieved by the telomerase complex, which is largely composed of telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC). A variety of mouse models have provided valuable insights into the relationship between the telomerase complex and telomere dysfunction at the organismal level and helped understand their biological significance in human. Recently, in addition to its role in maintenance of the telomeres, novel functions of the telomerase complex have been emerging. In this review, studies of all gene-targeted or transgenic mouse models so far generated for telomerase and telomere biology are comprehensively described, and potential novel functions of telomerase are briefly discussed
Animals ; Cell Aging/*physiology ; Mice ; Mice, Knockout ; Mice, Transgenic ; Models, Animal ; RNA/*metabolism ; Telomerase/*metabolism ; Telomere/*metabolism

SRG3 (SWI3-related gene) is a core subunit of mouse SWI/SNF complex and is known to play a critical role in stabilizing the SWI/SNF complex by attenuating its proteasomal degradation. SWI/SNF chromatin remodeling complex is reported to act as an important endogenous regulator in the proliferation and differentiation of mammalian neural stem cells. Because limited expression of SRG3 occurs in the brain and thymus during mouse embryogenesis, it was hypothesized that the altered SRG3 expression level might affect the process of adult hippocampal neurogenesis. Due to the embryonic lethality of homozygous knockout mice, this study focuses on dissecting the effect of overexpressed SRG3 on adult hippocampal neurogenesis. The BrdU incorporation assay, immunostaing with neuronal markers for each differentiation stage, and imunoblotting analysis with intracellular molecules involved in survival in adult hippocampal neurogenesis found no alteration, suggesting that the overexpression of SRG3 protein in mature neurons had no effect on the entire process of adult hippocampal neurogenesis including proliferation, differentiation, and survival.
Adult ; Animals ; Brain ; Bromodeoxyuridine ; Chromatin Assembly and Disassembly ; Embryonic Development ; Female ; Humans ; Mice ; Mice, Knockout ; Mice, Transgenic ; Neural Stem Cells ; Neurogenesis ; Neurons ; Pregnancy ; Thymus Gland

Osteocytes establish an extensive intracellular and extracellular communication system via gap junction-coupled cell processes and canaliculi, through which cell processes pass throughout bone, and the communication system is extended to osteoblasts on the bone surface. To examine the osteocyte function, several mouse models were established. To ablate osteocytes, osteocytes death was induced by diphtheria toxin. However, any types of osteocyte death result in necrosis, because dying osteocytes are not phagocytosed by scavengers. After the rupture of cytoplasmic membrane, immunostimulatory molecules are released from lacunae to bone surface through canaliculi, and stimulate macrophages. The stimulated macrophages produce interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-alpha), which are the most important proinflammatory cytokines triggering inflammatory bone loss. Therefore, the osteocyte ablation results in necrosis-induced severe osteoporosis. In conditional knockout mice of gap junction protein alpha-1 (GJA1), which encodes connexin 43 in Gap junction, using dentin matrix protein 1 (DMP1) Cre transgenic mice, osteocyte apoptosis and enhanced bone resorption occur, because extracellular communication is intact. Overexpression of Bcl-2 in osteoblasts using 2.3 kb collagen type I alpha1 (COL1A1) promoter causes osteocyte apoptosis due to the severe reduction in the number of osteocyte processes, resulting in the disruption of both intracellular and extracellular communication systems. This mouse model unraveled osteocyte functions. Osteocytes negatively regulate bone mass by stimulating osteoclastogenesis and inhibiting osteoblast function in physiological condition. Osteocytes are responsible for bone loss in unloaded condition, and osteocytes augment their functions by further stimulating osteoclastogenesis and further inhibiting osteoblast function, at least partly, through the upregulation of receptor activator of nuclear factor-kappa B ligand (RANKL) in osteoblasts and Sost in osteocytes in unloaded condition.
Animals ; Apoptosis ; Bone Resorption ; Cell Membrane ; Collagen Type I ; Connexin 43 ; Connexins ; Cytokines ; Dentin ; Diphtheria Toxin ; Gap Junctions ; Interleukin-6 ; Interleukins ; Macrophages ; Mice* ; Mice, Knockout ; Mice, Transgenic ; Necrosis ; Osteoblasts ; Osteocytes* ; Osteoporosis ; RANK Ligand ; Rupture ; Tumor Necrosis Factor-alpha ; Up-Regulation

The null mutation of cardiac Na+-Ca2+ exchanger (NCX1) gene in mice caused death of embryo in utero at embryonic day (ED) 9.0-9.5 and this embryonic lethality appears resulted from abnormal heart development. In the present study, we investigated whether transgenic re-expression of NCX1 in mutant cardiac myocytes could rescue these lethal defects. Transgenic mice expressing the canine NCX1 in a cardiac specific manner were bred into the NCX1 knock-out background but did not prevent the fetal lethality associated with the NCX1 null allele. However, the NCX1 knock-out embryos with an NCX1 transgene survived with heart beatings until ED 10.5 which was one day longer than the survival of the NCX1 knock-out embryos (ED 9.5). At ED 10.5, however, the partially rescued NCX1 embryos might have succumbed to the lack of an organized vasculature in the yolk sacs. The placental labyrinth layer was reduced in size and largely avascular. The transgenic re-expression of NCX1 rescued heart beatings and survived longer, but was still insufficient for the mice to be completely rescued. Importantly, NCX1 was observed to express in the yolk sac and the placenta of wild type mice. The results suggest that defects in extra-embryonic compartments are causal to the lethality, and that NCX1 may play an important role in establishing vascularization in extra-embryonic tissues.
Animals ; Embryo/*metabolism/pathology ; Embryo Loss ; Female ; Gene Deletion ; *Gene Expression ; Genetic Complementation Test ; Mice ; Mice, Knockout ; Mice, Transgenic ; Myocytes, Cardiac/metabolism ; Phenotype ; Placenta/metabolism/pathology ; Sodium-Calcium Exchanger/*genetics/*metabolism ; Survival Rate ; Yolk Sac/embryology/metabolism/pathology

Estrogens, a class of steroid hormones, regulate the growth, development, and physiology of the human reproductive system. Estrogens also involve in the neuroendocrine, skeletal, adipogenesis, and cardiovascular systems. Estrogen signaling pathways are selectively stimulated or inhibited depending on a balance between the activities of estrogen receptor (ER) alpha or ERbeta in target organs. ERs belong to the steroid hormone superfamily of nuclear receptors, which act as transcription factors after binding to estrogen. The gene expression regulation by ERs is to modulate biological activities, such as reproductive organ development, bone modeling, cardiovascular system functioning, metabolism, and behavior in both females and males. Understanding of the general physiological roles of ERs has been gained when estrogen levels were ablated by ovariectomy and then replenished by treatment with exogenous estrogen. This technique is not sufficient to fully determine the exact function of estrogen signaling in general processes in living tissues. However, a transgenic mouse model has been useful to study gene-specific functions. ERalpha and ERbeta have different biological functions, and knockout and transgenic animal models have distinct phenotypes. Analysis of ERalpha and ERbeta function using knockout mouse models has identified the roles of estrogen signaling in general physiologic processes. Although transgenic mouse models do not always produce consistent results, they are the useful for studying the functions of these genes under specific pathological conditions.
Adipogenesis ; Animals ; Animals, Genetically Modified ; Cardiovascular System ; Estrogen Receptor alpha ; Estrogen Receptor beta ; Estrogens ; Female ; Gene Expression Regulation ; Humans ; Male ; Mice ; Mice, Knockout ; Mice, Transgenic ; Ovariectomy ; Phenotype ; Receptors, Cytoplasmic and Nuclear ; Receptors, Estrogen ; Transcription Factors

Animals ; Lung ; Lung Diseases ; Mice ; Mice, Transgenic

Animals ; Lung ; Lung Diseases ; Mice ; Mice, Transgenic

Animals ; Lung ; Lung Diseases ; Mice ; Mice, Transgenic

Animals ; Lung ; Lung Diseases ; Mice ; Mice, Transgenic